Safety, Activity, and Biomarkers of SHR-1210, an Anti-PD-1 Antibody, for Patients with Advanced Esophageal Carcinoma

Clin Cancer Res. 2018 Mar 15;24(6):1296-1304. doi: 10.1158/1078-0432.CCR-17-2439. Epub 2018 Jan 22.


Purpose: The current management of advanced esophageal squamous cell carcinoma (ESCC) remains unsatisfactory. We investigated the safety, efficacy, and biomarkers of SHR-1210, an anti-PD-1 antibody, in patients with recurrent or metastatic ESCC.Experimental Design: This study was part of a phase I trial in China. Patients with advanced ESCC who were refractory or intolerant to previous chemotherapy were enrolled. Eligible patients received intravenous SHR-1210 at a dose of 60 mg, with escalation to 200 and 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. The associations between candidate biomarkers (PD-L1 and somatic mutation load) and the efficacy of SHR-1210 were also explored.Results: Between May 11, 2016, and December 9, 2016, a total of 30 patients from one site in China were enrolled. Ten patients (33.3%) had an independently assessed objective response. Median progression-free survival was 3.6 months (95% CI, 0-7.2). Three (10.0%) treatment-related grade 3 adverse events were reported: two (6.7%) pneumonitis and one (3.3%) increased cardiac troponin I. No grade 4 or grade 5 treatment-related adverse events were reported. The exome sequencing and analysis showed that the mutational burden and the potential mutation-associated neoantigen count were associated with better responses. An objective response was more common in patients with PD-L1-positive tumors as defined by ≥5% staining (7 of 15 patients) than in those with PD-L1-negative tumors (1 of 9 patients).Conclusions: In this population of ESCC patients, SHR-1210 had a manageable safety profile and promising antitumor activity. Clin Cancer Res; 24(6); 1296-304. ©2018 AACR.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / genetics
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Programmed Cell Death 1 Receptor
  • camrelizumab